DESCRIPTION: This renewal application proposes to study in-depth the cell and molecular biology of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), a cell-cell adhesion molecular of the immunoglobulin gene superfamily that is expressed on endothelial cells, platelets and leukocytes, and was originally described by the Applicant. Studies of the regulation of the adhesive activity and expression of PECAM-1 are proposed. Specifically, experiments are planned to identify specific regions of the extracellular domain of PECAM- 1 that are involved in both homophilic and heterophilic PECAM-1 mediated interactions. The second series of studies will examine the role of posttranslational changes in the cytoplasmic domain of PECAM-1 (specifically phosphorylation and palmitoylation), effected by site- directed mutagenesis, in the control of the subcellular distribution and adhesive properties of the molecule. Finally, a series of experiments is proposed to characterize the regulatory domains within the recently defined PECAM-1 promoter.